SAPFIR: A webserver for the identification of alternative protein features

Background: Alternative splicing can increase the diversity of gene functions by generating multiple isoforms with different sequences and functions. However, the extent to which splicing events have functional consequences remains unclear and predicting the impact of splicing events on protein activity is limited to gene-specific analysis. Results: To accelerate the identification of functionally relevant alternative splicing events we created SAPFIR, a predictor of protein features associated with alternative splicing events. This webserver tool uses InterProScan to predict protein features such as functional domains, motifs and sites in the human and mouse genomes and link them to alternative splicing events. Alternative protein features are displayed as functions of the transcripts and splice sites. SAPFIR could be used to analyze proteins generated from a single gene or a group of genes and can directly identify alternative protein features in large sequence data sets. The accuracy and utility of SAPFIR was validated by its ability to rediscover previously validated alternative protein domains. In addition, our de novo analysis of public datasets using SAPFIR indicated that only a small portion of alternative protein domains was conserved between human and mouse, and that in human, genes involved in nervous system process, regulation of DNA-templated transcription and aging are more likely to produce isoforms missing functional domains due to alternative splicing. Conclusion: Overall SAPFIR represents a new tool for the rapid identification of functional alternative splicing events and enables the identification of cellular functions affected by a defined splicing program. SAPFIR is freely available at https://bioinfo-scott group.med.usherbrooke.ca/sapfir/, a website implemented in Python, with all major browsers supported. The source code is available at https://github.com/DelongZHOU/ SAPFIR.

Automated summary

SAPFIR is a predictor of protein features associated with alternative splicing events, allowing for rapid identification of functional alternative splicing events and analysis of proteins generated from diverse genes, providing guidance on the impact on cellular functions.